Claims for Patent: 11,986,444

Summary for Patent: 11,986,444

Title:	Treatment of poor metabolizers of dextromethorphan with a combination of bupropion and dextromethorphan
Abstract:	Disclosed herein is a method of safely treating a nervous system condition with a combination of dextromethorphan and bupropion. This method is intended for patients having a neurological condition or a psychiatric condition, such as major depressive disorder, and a CYP2D6 poor metabolizer genotype or a CYP2D6 poor metabolizer phenotype.
Inventor(s):	Herriot Tabuteau
Assignee:	Antecip Bioventures II LLC
Application Number:	US18/488,366
Patent Claims:	1. A method of treating major depressive disorder in a CYP2D6 poor metabolizer comprising, selecting a human patient known to be a poor CYP2D6 metabolizer who is experiencing major depressive disorder, and administering, once daily in the morning for at least two weeks to the human patient, a dosage form containing 1 mg to 105 mg of bupropion hydrochloride, or a molar equivalent amount of the free base or another salt form of bupropion and 1 mg to 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of the free base or another salt form of dextromethorphan, wherein the dextromethorphan AUC0-12 of the human patient is increased 208% to 557% compared to extensive or ultra-extensive CYP2D6 metabolizers. 2. The method of claim 1, wherein the dextromethorphan AUC0-12 of the human patient is increased 340% compared to extensive or ultra-extensive CYP2D6 metabolizers. 3. The method of claim 1, wherein approximately 26% of the dextromethorphan is excreted unchanged in the urine of the human patient. 4. The method of claim 1, wherein a combination of 105 mg of bupropion hydrochloride and 45 mg of dextromethorphan hydrobromide is present in a solid dosage form. 5. The method of claim 1, wherein once-daily administration for 8 days avoids the human patient having an about 3.4-fold increase in the AUC0-12 of dextromethorphan as compared to the AUC0-12 of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer. 6. The method of claim 1, wherein once-daily administration for 8 days avoids the human patient having an about 3-fold increase in the Cmax of dextromethorphan as compared to the Cmax of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer. 7. The method of claim 1, wherein the dextromethorphan is in an immediate-release formulation. 8. The method of claim 7, wherein the bupropion is in an extended-release formulation. 9. The method of claim 1, wherein the dosage form further contains a carbomer homopolymer and colloidal silicon dioxide. 10. The method of claim 1, wherein the dosage form further contains crospovidone and glyceryl monocaprylocaprate. 11. The method of claim 1, wherein the dosage form further contains L-cysteine hydrochloride monohydrate. 12. The method of claim 1, wherein the dosage form further contains magnesium stearate and microcrystalline cellulose. 13. The method of claim 1, wherein the dosage form further contains polyvinyl alcohol and sodium lauryl sulfate. 14. The method of claim 1, wherein the dosage form further contains red iron oxide and stearic acid. 15. The method of claim 1, wherein the dosage form further contains talc, titanium dioxide, or yellow iron oxide. 16. The method of claim 1, wherein twice-daily administration of the dosage form to the human patient for 8 days would result in the human patient having about same AUC0-12 of bupropion as compared to the AUC0-12 of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer. 17. The method of claim 1, wherein twice-daily administration of the dosage form to the human patient for 8 days would result in the human patient having about same Cmax of bupropion as compared to the Cmax of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer. 18. A method of treating major depressive disorder in a CYP2D6 poor metabolizer comprising, selecting a human patient known to be a poor CYP2D6 metabolizer who is experiencing major depressive disorder, and administering, once daily in the morning for at least four weeks to the human patient, a dosage form containing 1 mg to 105 mg of bupropion hydrochloride, or a molar equivalent amount of the free base or another salt form of bupropion and 1 mg to 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of the free base or another salt form of dextromethorphan, wherein the dextromethorphan AUC0-12 of the human patient is increased 208% to 557% compared to extensive or ultra-extensive CYP2D6 metabolizers. 19. The method of claim 18, wherein the dextromethorphan AUC0-12 of the human patient is increased 340% compared to extensive or ultra-extensive CYP2D6 metabolizers. 20. The method of claim 18, wherein approximately 26% of the dextromethorphan is excreted unchanged in the urine of the human patient. 21. The method of claim 18, wherein the dextromethorphan is in an immediate-release formulation. 22. The method of claim 21, wherein the bupropion is in an extended-release formulation. 23. The method of claim 18, wherein the dosage form further contains a carbomer homopolymer and colloidal silicon dioxide. 24. The method of claim 18, wherein the dosage form further contains crospovidone and glyceryl monocaprylocaprate. 25. The method of claim 18, wherein the dosage form further contains L-cysteine hydrochloride monohydrate. 26. The method of claim 18, wherein the dosage form further contains magnesium stearate and microcrystalline cellulose. 27. The method of claim 18, wherein the dosage form further contains polyvinyl alcohol and sodium lauryl sulfate. 28. The method of claim 18, wherein the dosage form further contains red iron oxide and stearic acid.